6-Methoxy-1H-indazole → N-tert-butyl-2-(6-methoxy-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246500

Reaction equation

HRID 246500 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:9][N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:5]2=[N:6][CH:7]=1.[CH3:26][O:27][C:28]1[CH:36]=[C:35]2[C:31]([CH:32]=[N:33][NH:34]2)=[CH:30][CH:29]=1.CC(C)([O-])C.[Na+]>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[C:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([N:34]3[C:35]4[C:31](=[CH:30][CH:29]=[C:28]([O:27][CH3:26])[CH:36]=4)[CH:32]=[N:33]3)[N:3]=2)[N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=1)=[O:12])([CH3:17])([CH3:16])[CH3:15]

Participants

6

Reactant 3

HCID 126392026-Methoxy-1H-indazoleHCID 23676156Sodium t-butoxideHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 71279780N-tert-butyl-2-(6-methoxy-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 57%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
125 °C

Procedure

To a stirred solution of 2-bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (200 mg, 468 μmol), 6-methoxy-1H-indazole (69.3 mg, 468 μmol) in dioxane (3.5 mL) was added sodium tert-butoxide (98.9 mg, 1.03 mmol) and bis(tri-tert-butylphosphine)palladium(0) (23.9 mg, 46.8 μmol). The mixture was degassed then heated in sealed tube at 125° C. for two days. The mixture was cooled, filtered through celite, the cake washed with ethyl acetate, and the combined filtrates were concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-30% ethyl acetate in hexanes) gave N-tert-butyl-2-(6-methoxy-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (131 mg, 57%). 1H NMR (CDCl3) δ: 9.06 (s, 1H), 8.33 (s, 1H), 8.18 (d, J=0.8 Hz, 1H), 7.95 (d, J=2.0 Hz, 1H), 7.80 (s, 1H), 7.73 (d, J=8.8 Hz, 1H), 7.01 (dd, J=8.8, 2.3 Hz, 1H), 5.71 (s, 2H), 3.94 (s, 3H), 3.53-3.63 (m, 2H), 1.57 (s, 9H), 0.91-0.98 (m, 2H), −0.03 (s, 9H).

Workup

  1. customThe mixture was degassed
  2. temperatureThe mixture was cooled
  3. filtrationfiltered through celite
  4. washthe cake washed with ethyl acetate
  5. concentrationthe combined filtrates were concentrated in vacuo
  6. customPurification by chromatography (silica, 24 g Analogix column, 0-30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-98cdff4016da4457b4403441681f80f2
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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